Newborn hearing screening in Hong Kong.

OBJECTIVES: To review studies on newborn hearing screening in Hong Kong and the current evidence on the cost-effectiveness of universal newborn hearing screening programmes and to determine their value and the best model for such a programme in Hong Kong. DATA SOURCE: Medline literature search (1985-2004), local reports and abstracts available to the author. STUDY SELECTION: Literature and data on newborn hearing screening strategies, screening devices, cost-effectiveness study of universal newborn hearing screening programmes. DATA EXTRACTION: Relevant information and data were reviewed by the author. DATA SYNTHESIS: A universal newborn hearing screening programme with a high coverage rate is essential to enable early diagnosis and intervention before 6 months of age. This ensures good language and cognitive outcomes in hearing impaired children. A cost-effective universal newborn hearing screening programme should be hospital-based to achieve a high coverage rate, use modern screening devices with high sensitivity and specificity that enable early diagnosis, and be acceptable to parents. CONCLUSIONS: Increasing evidence supports the cost-effectiveness and long-term benefits of universal newborn hearing screening programmes. The medical community in Hong Kong should work towards the development and implementation of a well-coordinated, collaborative, multidisciplinary, cost-effective, and sustainable territory-wide universal newborn hearing screening programme coupled with interventions for the next generation of hearing impaired children.

Splenic rupture in a premature neonate.

Splenic injuries are very rare in neonates. We report a case of splenic injury in a premature neonate, highlighting the importance of a high-index suspicion in early recognition of this rare but potentially fatal intra-abdominal injury. We also review the literature on possible aetiologies and mechanism of splenic injury, as well as its management. This is the first reported case of a very low-birth-weight neonate with splenic rupture who survived with intact neurology.

Feasibility of implementing a universal neonatal hearing screening programme using distortion product otoacoustic emission detection at a university hospital in Hong Kong.

OBJECTIVE: To assess the feasibility of implementing a universal neonatal hearing screening programme using distortion product otoacoustic emission detection at a major teaching hospital in Hong Kong. DESIGN: Descriptive study and questionnaire. SETTING. Teaching hospital, Hong Kong. METHODS: A total of 1064 infants, together with their mothers, were successfully recruited for the study. The participation rate was 99.3%. A three-stage hearing screening protocol using distortion product otoacoustic emission detection was adopted. Each of the participating infants was screened on three separate occasions (day 1-4, day 5-14, and day 21-30 after birth), irrespective of the test results. A questionnaire was administered to 364 randomly selected mothers to determine whether as consumers of the hearing screening service, mothers would find screening desirable. RESULTS: Results of the screening demonstrated an incidence of permanent bilateral hearing loss (>or=40 dB in the better ear) of 0.28%. The results also showed that 3.5% of the screened infants were referred for subsequent diagnostic audiological assessment, including those suspected with unilateral as well as bilateral hearing loss. Data obtained were comparable to other reported results obtained using multi-stage screening protocols. Taking both the false positive rate and the default rate into consideration, the most appropriate time for screening in this hospital setting appeared to be around day 5 to 14 when infants returned to the hospital's day centre as out-patients for routine medical follow-up. Since this day centre service is not generally provided by all maternity hospitals in Hong Kong, an alternative time for screening would be around day 21 to 30 when infants could return as out-patients solely for the hearing test. The results of the questionnaire suggested that most mothers thought a neonatal hearing screening would be desirable (91.35%). The majority (81.70%) indicated a preference for screening either within a few days of birth at the maternity ward prior to discharge from the hospital, or between 5 and 30 days when returning to the hospital as an out-patient. CONCLUSION: It was concluded that a universal neonatal hearing screening programme could be readily implemented in a maternity hospital setting in Hong Kong.

MRI of neonatal encephalopathy.

We present the magnetic resonance imaging (MRI) findings in neonatal encephalopathy, including hypoxic-ischaemic encephalopathy, perinatal/neonatal stroke, metabolic encephalopathy from inborn errors of metabolism, congenital central nervous system infections and birth trauma. The applications of advanced MRI techniques, such as diffusion-weighted imaging and magnetic resonance spectroscopy are emphasized.

Role of SH3 domain-containing proteins in clathrin-mediated vesicle trafficking in Arabidopsis.

A group of plant AtSH3Ps (Arabidopsis thaliana SH3-containing proteins) involved in trafficking of clathrin-coated vesicles was identified from the GenBank database. These proteins contained predicted coiled-coil and Src homology 3 (SH3) domains that are similar to animal and yeast proteins involved in the formation, fission, and uncoating of clathrin-coated vesicles. Subcellular fractionation and immunolocalization studies confirmed the presence of AtSH3P1 in the endomembrane system. In particular, AtSH3P1 was localized on or adjacent to the plasma membrane and its associated vesicles, vesicles of the trans-Golgi network, and the partially coated reticulum. At all of these locations, AtSH3P1 colocalized with clathrin. Functionally, in vitro lipid binding assay demonstrated that AtSH3P1 bound to specific lipid groups known to accumulate at invaginated coated pits or coated vesicles. In addition, immunohistochemical studies and actin binding assays indicated that AtSH3P1 also may regulate vesicle trafficking along the actin cytoskeleton. Yeast complementation studies suggested that AtSH3Ps have similar functions to the yeast Rvs167p protein involved in endocytosis and actin arrangement. A novel interaction between AtSH3P1 and an auxilin-like protein was identified by yeast two-hybrid screening, immunolocalization, and an in vitro binding assay. The interaction was mediated through the SH3 domain of AtSH3P1 and a proline-rich domain of auxilin. The auxilin-like protein stimulated the uncoating of clathrin-coated vesicles by Hsc70, a reaction that appeared to be inhibited in the presence of AtSH3P1. Hence, AtSH3P1 may perform regulatory and/or scaffolding roles during the transition of fission and the uncoating of clathrin-coated vesicles.

Genotoxicity of human breast milk from different countries.

Dietary and/or environmental factors appear to play a key role in the international variations that exist in breast cancer incidence. The genotoxicity of breast milk extracts is being examined as a possible indicator of in vivo exposure of mammary epithelial cells to DNA-damaging agents. Breast milk samples were obtained from the UK (n = 32), a high risk country, and from Hong Kong (n = 10), India (n = 20) and Singapore (n = 20), countries of lower breast cancer incidence. The abilities of breast milk extracts to induce DNA damage detected as single-strand breaks (SSBs) in the alkaline Comet assay and to induce micronuclei in MCL-5 cells and mutations in Salmonella typhimurium YG1019 were investigated. In the Comet assay 18 of 32 (56%) UK samples induced significant increases in DNA SSBs compared with 2 of 10 (20%), 5 of 20 (25%) and 8 of 20 (40%) of the samples from Hong Kong, India and Singapore, respectively. The proportion of positive samples was significantly higher in the UK group than in the combined low breast cancer incidence group and significantly higher than in the Indian group (P < 0.05, Fisher's exact test). In the micronucleus assay 9 of 32 (28%) UK samples showed significant activity compared with 0 of 10 (0%), 2 of 20 (10%) and 3 of 20 (15%) of the samples from Hong Kong, India and Singapore, respectively. Extracts of all the aforementioned milk samples were also tested for bacterial mutagenicity. Nine of 32 (28%) UK samples induced significant activity with a dose-response effect. Although activity was detected in samples from the other countries, comparable dose-response data could not be obtained because of a lack of material. This pilot study suggests that genotoxic components occur more frequently in UK breast milk than in milk from some other countries with a lower incidence of cancer. More work is required to confirm these initial findings and to examine their relevance to variations in breast cancer incidence.

Surfactant tracheobronchial lavage for the management of a rabbit model of meconium aspiration syndrome.

We evaluated the effect of tracheobronchial lavage with diluted surfactant solution (bovine lipid extract surfactant, bLES) in a rabbit model of meconium aspiration. All animals were anaesthetized, tracheotomized and given 3-4 ml/kg of 25% slurry of human meconium into the endotracheal tube and mechanically ventilated for 1 h. The animals were then randomly assigned to surfactant lavage (n = 12) with 15 ml/kg of diluted surfactant at a concentration of 5.4 mg phospholipid/ml administered in aliquots of 2 ml; or simple endotracheal suction (control n = 12) when the oxygenation index (OI) was >/=15. Changes in the arterial blood gases and the histomorphological and radiological appearances of the lungs were recorded. The OI and arterial/alveolar oxygen tension (a/A PO2) of the surfactant lavage group improved significantly at 5 min post-treatment, and these improvements were observed throughout the ensuing 4 h of ventilation. There was significantly more solid content recovered by surfactant lavage compared with the control group (p = 0.0001). Radiologically, the post-treatment air space opacification scores of the lavage group were significantly lower compared with the control (p = 0.002). The post-treatment radiographs of the lavage-treated rabbits were rated by the radiologist, who was blinded to the treatment groups, as much improved in 5 and improved in 4, whereas the control rabbits were rated as much worse in 3 and worse in 4. Histological examination showed the lungs of the lavaged rabbits had significantly more normal airway (p < 0.0001), more fields showing completely normal airspace (p = 0.0001) and less fields showing severe overdistension with meconium (p = 0.0005). We concluded that lavage with diluted surfactant solution effectively washed out the meconium, improved gases exchanges, and improved the histological and radiological appearances in the rabbit model of MAS.

Variable levels of mosaicism for trisomy 21 in a non-immune hydropic infant with chylothorax.

We report the first case of mosaic trisomy 21 with non-immune hydrops fetalis and bilateral chylothoraces. Prenatal fetal blood karyotype analysis of 15 fetal cells revealed a 46,XX karyotype. Aggressive prenatal management, including fetal thoracocentesis and pleuro-amniotic shunt, was performed. A clinical phenotype of Down syndrome was apparent after the gross oedema had subsided. Subsequent chromosome study of neonatal blood lymphocytes showed mosaic trisomy 21 with 23 per cent trisomic cells. Review of the initial fetal blood sample identified trisomy in 5 per cent of 134 cells. Follow-up study at five months showed no trisomy 21 in 100 cells. This case illustrates the variable levels of mosaicism manifest in the peripheral blood of an infant with obvious Down syndrome phenotype, and the limitation of cytogenetic analysis of peripheral lymphocytes alone in prenatal and postnatal detection of low levels of mosaicism.

Surfactant lavage for the management of severe meconium aspiration syndrome.

Meconium aspiration syndrome (MAS) continues to be a major cause of morbidity and mortality in newborn infants. Recent studies on the pathophysiology of MAS showed that the meconium is more potent and toxic than we had previously appreciated. On the basis of animal experiences and a clinical pilot study, we propose that early tracheobronchial lavage with diluted surfactant is an effective and safe method for treatment of severe MAS.

Surfactant lavage for meconium aspiration syndrome: a pilot study.

OBJECTIVE: Meconium aspiration syndrome (MAS) is a major cause of respiratory morbidity and mortality in term infants. We reported our pilot experience on the use of diluted bovine lung surfactant lipid extract solution (Survanta [Ross Laboratories, Ohio, USA]) as a tracheobronchial lavage fluid for the treatment of infants with severe MAS. Our goal was to establish the safety and the effectiveness of this procedure before organizing a randomized controlled trial. METHOD: Six infants with severe MAS necessitating mechanical ventilation with an oxygen index of >/=15 within 6 hours of life recruited consecutively during a 11/2-year period were treated with tracheobronchial lavage with 15 mL/kg of diluted surfactant solution (Survanta) at a phospholipid concentration of 5 mg/mL administered in 2-mL aliquots. The outcome of treatment was assessed by comparison with 6 consecutive historic control infants with equally severe MAS of similar inclusion criteria retrospectively. RESULTS: The mean oxygen index, mean airway pressure, fraction of inspired oxygen, and arterial/alveolar oxygen tension ratio improved significantly within the first 48 hours after treatment in the lavage group. The duration of ventilation (mean +/- SEM, 55.3 +/- 4.6 hours vs 131 +/- 60 hours) and oxygen therapy (mean +/- SEM, 4.1 +/- 0.5 days vs 20.8 +/- 8.2 days) were also significantly reduced in the lavage-treated group compared with the control group. All 6 patients in the lavage group survived without sequelae whereas there were 2 deaths in the control group. The process of administering the surfactant lavage was well tolerated with no air leak complications. CONCLUSIONS: Our experience suggested that surfactant lavage seems to be an effective and safe method for treatment of severe MAS. A multicenter randomized control trial is indicated to further study the efficacy of this treatment.

The timing of early postnatal catch-up growth in normal, full-term infants born short for gestational age.

Postnatal catch-up growth in infants born small for gestational age has been reported to occur mainly during the initial 3-9 months of life. The study presented here characterized early postnatal growth in healthy, full-term infants born short for gestational age (GA) (< -2 standard deviation scores [SDS] in birth length) in two populations. Results from a longitudinal growth study from birth to final height of 139 infants born short for GA between 1973 and 1975 in Göteborg, Sweden, were compared with results from an ongoing detailed prospective 6-month follow-up of 41 Hong Kong Chinese infants born short for GA in 1995 and 1996. For both populations, height was expressed in SDS using the updated Swedish growth reference data at birth and postnatally. In the Swedish study, 92% of the children born short for GA reached a final height greater than -2 SDS; 76% had a height greater than -2 SDS by 2 months of age. In the Hong Kong study, 79% reached a height greater than -2 SDS by 5 months of age (the longest follow-up time to date). A third population of Hong Kong Chinese infants born short for GA in 1967 was studied; 65% had reached the normal height range by 5 months of age. In the later Hong Kong study (1995-1996), catch-up growth could be identified as early as 12 weeks of age, which has important implications for clinical practice. Thus, growth monitoring during the first weeks of postnatal life gives useful information on catch-up growth in infants born short for GA.

Decreased bone carbonate content in response to metabolic, but not respiratory, acidosis.

In vitro cultured neonatal mouse calvariae release calcium and buffer the medium proton concentration in response to a decrease in the medium pH caused by a reduction in bicarbonate concentration ([HCO3-]), a model of metabolic acidosis, but not to an equivalent decrease in pH caused by an increase in the partial pressure of carbon dioxide (PCO2), a model of respiratory acidosis. We have postulated that the medium is in equilibrium with the carbonated apatite in bone. To determine whether bone carbonate is depleted during models of acidosis, we cultured calvariae in control medium (pH approximately 7.4, PCO2 approximately 43, [HCO3-] approximately 26) or in medium in which the pH was equivalently reduced by either a decrease in [HCO3-] (metabolic acidosis, pH approximately 7.1, [HCO3-] approximately 13) or an increase in PCO2 (respiratory acidosis, pH approximately 7.1, PCO2 approximately 86) and determined net calcium flux (JCa) and bone carbonate content. We found that compared with control, after 3, 24, and 48 h there was a decrease in bone carbonate content during metabolic but not during respiratory acidosis. Compared with control, at 3 h JCa increased with both respiratory and metabolic acidosis; however, at 24 and 48 h JCa increased only with metabolic acidosis. JCa was correlated inversely with percent bone carbonate content in control and metabolic acidosis at all time periods studied (r = -0.809, n = 23, P < 0.001). Thus a model of metabolic acidosis appears to increase JCa from bone, perhaps due to the low [HCO3-] inducing bone carbonate dissolution.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome and management of babies with prenatal ultrasonographic renal abnormalities.

Between January 1987 and December 1990, 60 fetuses were found to have renal abnormalities on antenatal ultrasonography. Six fetuses were aborted because of major renal abnormalities with or without associated chromosomal aberrations. Twelve babies with major renal abnormalities died in the immediate neonatal period. Forty-two babies were studied after birth and followed up. Babies who were found to have mild dilation of the renal pelvis of 6 to 10 mm during fetal life revealed either normal renal findings in the postnatal period or complete resolution of the abnormalities within the first year. Significant pelvic dilation of more than 10 mm occurred in 32 babies. A significant proportion (34%) had transitional hydronephrosis that resolved spontaneously during the follow-up period (mean, 2 1/2 years; range, 1 1/2 to 4 1/2 years). Extrarenal pelvis, another benign condition, accounted for 15.6%. Most babies with pelviureteral junction obstruction (15%) and vesicoureteral junction obstruction (6.2%) required early neonatal surgery. The technetium-99m diethylenetriamine renal scan with the diuretic renogram half-time was found to be a very useful tool to distinguish between obstructive and nonobstructive hydronephrosis. With early diagnosis and intervention, the prognosis for many of these renal abnormalities is much more favorable and such information is invaluable for antenatal counseling.

Perinatal features of birth asphyxia and neurologic outcome.

The perinatal events of 40 term newborn infants who had severe birth asphyxia were reviewed and correlated with the neurological outcome at a mean age of 2 1/2 years. Severe birth asphyxia was defined as an Apgar Score of less than or equal to 3 at 1 min. The majority (68.5%) of the babies had an abnormal fetal heart pattern before delivery. Persistent fetal bradycardia was most frequently associated with poor outcome. The neurological staging, the need for assisted ventilation for more than 24 hours and severe renal impairment were the best predictors of neonatal death or subsequent poor neurological outcome. The overall mortality was 10% and 15% of the surviving babies had varying degrees of neurological handicap.

Effect of indomethacin on binding of bilirubin to albumin.

The effect of indomethacin on the binding of bilirubin to protein was studied in vitro by the horseradish peroxidase oxidation method. Plasma indomethacin concentrations ranging from 1500 micrograms/l to 4500 micrograms/l, which were much higher than the therapeutic concentrations achieved in vivo, were used for the studies. The bilirubin-protein titration curves obtained indicate that indomethacin, although protein bound, does not affect the binding of bilirubin to protein. Our study confirms that it is safe to use conventional doses of indomethacin in jaundiced preterm infants.

Nosocomial gastroenteritis in paediatric patients.

Between November 1982 and April 1985, 2228 children under the age of 5 years with acute gastroenteritis were admitted to the paediatric isolation ward of Queen Mary Hospital, Department of Paediatrics, University of Hong Kong. In 56.2% the causative agent was identified as rotavirus, Salmonella, Campylobacter, Shigella, Escherichia coli or a combination of these pathogens. Our isolation procedures included cohort nursing of all diarrhoeal patients in two separate rooms (each accommodating 6 patients), barrier gowns and stringent handwashing with chlorhexidine. A total of 163 cases (13.4% of all positive cases) were identified as nosocomial infections. Rotavirus was the responsible agent for nosocomial infection in 128 cases (20% of all rotavirus infection). There were 35 patients with bacterial nosocomial infection, (7% of all the bacterial positive cases). Nosocomial rotavirus gastroenteritis was 3.4 times more frequent than nosocomial gastroenteritis due to bacterial pathogens. We conclude that modification of our present isolation procedures is necessary in order to reduce rotavirus nosocomial infection.

Salmonella meningitis in infancy.

Despite adequate treatment, mortality and morbidity were high among the 13 cases of Salmonella meningitis in this series. Chloramphenicol, being a bacteriostatic agent against Salmonella species, is not a suitable antibiotic for the treatment of Salmonella meningitis. Treatment for 4-6 weeks is recommended with use of an antibiotic capable of achieving an adequate bactericidal concentration in the cerebrospinal fluid such as moxalactam. Intraventricular antibiotic treatment should be considered if there is a delay in the eradication of the Salmonella organisms from the cerebrospinal fluid after starting treatment.